Hemoglobin A1c, a binding product of glucose and hemoglobin, increases depending on the severity of hyperglycemia in a glucose level-dependent manner. Because hemoglobin A1c once produced is not eliminated until the lifetime of erythrocyte (120 days) runs out, it reflects the past blood glucose control conditions over a long period of time (Non-patent document 1). Hemoglobin A1c was adopted as a selected test item of the basic health screening according to the Health Law for the Aged since 1996 and adopted as an auxiliary diagnosis indicator of diabetes mellitus in the new diagnosis criteria of diabetes mellitus in 1999. Therefore, it is considered that hemoglobin A1c is an indicator of great clinical significance (Non-patent document 2).
If a hyperglycemic condition is sustained, glucose specific insulin hyposecretion and insulin resistance are observed and serve as factors that further aggravate hyperglycemia (Non-patent document 3). Because long-term blood glucose level control is necessary to prevent progression from the hyperglycemic condition to onset of diabetes mellitus, it is considered to become necessary to suppress increase in the hemoglobin A1c level. Alimentotherapies and exercise are recommended to control blood glucose level in patients with prediabetes (condition suspected of diabetes). Although various functional foods for preventing postprandial increases in blood glucose level (food for specified health uses) have already been marketed, all of these only have a temporary effect of suppressing increase in blood glucose level. Therefore, control of blood glucose level over a long period of time cannot be expected, and development of such a substance having a hemoglobin A1c level lowering action has been desired.
Furthermore, α-glucosidase inhibitors, sulfonylurea drugs as insulin secretagogues, thiazolidine derivatives as insulin resistance improving agents and so forth are currently used as therapeutic agents for diabetes mellitus. However, the drug efficacies thereof are not satisfactory, and they suffer many problems such as side effects causing coma due to rapid drop in blood glucose level.
Under the aforementioned circumstances, discovery of a substance that can be safely ingested without causing hypoglycemia and has a long-term blood glucose level control action by decreasing the hemoglobin A1c level has been strongly desired.
Conventionally, as examples of substances having an effect of suppressing increases in blood glucose level, the prior art references have disclosed a hyperglycemia suppressing agent containing a banaba-derived ingredient (Patent document 1), a hyperglycemia suppressing agent containing a concentrated extract of fermentation product of wheats or barleys as an active ingredient (Patent document 2) and so forth.
Furthermore, as techniques of using a triterpene glycoside as an active ingredient, for example, a diabetes preventing agent containing a glycoside extracted from Gymnema inodorum as an active ingredient (Patent document 3), a metabolism improving method and a composition therefor containing corosolic acid extracted from banaba as an active ingredient (Patent document 4), a lipase inhibitor (Patent document 5) and a triterpene derivative having an immunosuppressing activity (Patent document 6) have been disclosed.
Furthermore, it has been disclosed that the insulin action enhancing activity of a compound having a lanostane skeleton or 3,4-secolanostane skeleton (Patent document 7) enhances the insulin action in regulation of adipocyte differentiation, although the effect thereof on diseases in the pancreas is unknown.
Furthermore, compounds selected from the group consisting of 24-alkylcholesten-3-ones and 24-alkylcholestan-3-ones that have no double bond in the basic steroid skeleton have been disclosed as hypoglycemic agents (Patent document 8).
Meanwhile, lophenol (one of the stereoisomers of 4-methylcholest-7-en-3-ol) has been known to be an intermediate of the biosynthetic pathway starting from squalane in plants (Non-patent document 4). As for prior arts of this compound, however, there is only a reference concerning the biosynthetic system of lophenol (Non-patent document 5), and the use of the compound is not known at all.
The genus Aloe in the family Liliaceae is a group of plants including Aloe vera (Aloe barbadensis Miller) and Aloe arborescens (Aloe arborescens Miller var. natalensis Berger) and so forth, and they are empirically known to have various efficacies. The prior arts regarding the use of plants of the genus Aloe include immunomodulating polysaccharides (Patent document 9), immunosuppression improving agents containing a butanol fraction of an aloe extract or aloin (Patent document 10), HSP60 family protein synthesis suppressing agents containing aloin derivatives (Patent documents 11 to 13), protein having lectin activity derived from aloe leaf-skin (Patent document 14) and so forth.
As the prior arts regarding improvement of blood glucose levels by the plants of the genus Aloe, clinical studies in the United States (Non-patent document 6) and a hypoglycemic action observed in animal studies (Non-patent documents 7 and 8) and polysaccharides in plants of the genus Aloe (Patent document 15) have been disclosed. In these prior arts, the hypoglycemic ingredients of the plants of the genus Aloe were predicted to be polysaccharides or glycoproteins. Furthermore, it has been disclosed that, in a pressed extract of Aloe vera and a hypoglycemic agent containing the extract as an active ingredient (Patent document 16), a characteristic peak unique to an ester group observed in the FT-IR chart correlates with the activity, that the active ingredient is a polysaccharide, amino acid, malic acid or the like, and that the aforementioned active ingredient is degraded in commercially available Aloe vera gel powders, Aloe vera gel solutions and Aloe vera gel extracts. Furthermore, in addition to the above, a hypoglycemic action of aloe polysaccharides (Patent document 17) and antioxidative action of 7-hydroxychromone contained in aloe (Patent document 18) have been disclosed.    [Patent document 1] Japanese Patent Laid-open (Kokai) No. 2003-095941    [Patent document 2] Japanese Patent Laid-open No. 2002-371003    [Patent document 3] Japanese Patent Laid-open No. 05-247086    [Patent document 4] Japanese Patent Laid-open No. 2002-205949    [Patent document 5] Japanese Patent Laid-open No. 09-040689    [Patent document 6] International Patent Unexamined Publication in Japanese (Kohyo) No. 11-511482    [Patent document 7] Japanese Patent Laid-open No. 10-330266    [Patent document 8] Japanese Patent Laid-open No. 2003-048837    [Patent document 9] International Patent Application Unexamined Publication in Japanese No. 2001-520019    [Patent document 10] Japanese Patent Laid-open No. 08-208495    [Patent document 11] Japanese Patent Laid-open No. 10-120576    [Patent document 12] Japanese Patent Laid-open No. 10-045604    [Patent document 13] Japanese Patent Laid-open No. 10-036271    [Patent document 14] Japanese Patent Laid-open No. 09-059298    [Patent document 15] Japanese Patent Laid-open No. 60-214741    [Patent document 16] Japanese Patent Laid-open No. 2003-286185    [Patent document 17] U.S. Pat. No. 4,598,069    [Patent document 18] U.S. Patent Application Publication No. 2003/0207818    [Non-patent document 1] Nippon Rinsho, No. 748, Vol. 1, pp. 615-617, 1999    [Non-patent document 2] Nippon Rinsho, No. 808, Vol. 2, pp. 405-409, 2002    [Non-patent document 3] Yazaki Y. & Muramatsu M. Ed., “Front Line of Diabetes Mellitus,” pp. 126-139, Yodosha, 1997    [Non-patent document 4] Yamada A., “Experimental Methods of Biochemistry”, Vol. 24, Experimental Methods for Fat and Lipid Metabolism, p. 174, Gakkai Shuppan Center, 1989    [Non-patent document 5] Chem. Pharm. Bull., pp. 624-626, 1993    [Non-patent document 6] Phytomedicine, Vol. 3, pp. 245-248, 1996    [Non-patent document 7] Phytotherapy Research, Vol. 15, pp. 157-161, 2001    [Non-patent document 8] Phytotherapy Research, Vol. 7, pp. 37-42, 1993